Heat shock factor 2 is a stress‐responsive mediator of neuronal migration defects in models of fetal alcohol syndrome

Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal andHsf2‐deficient mice and cell systems to uncover a pivotal role for heat shock factor 2 (HSF2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF2 is essential for the triggering of HSF1 activation, which is accompanied by distinctive post‐translational modifications, and HSF2 steers the formation of atypical alcohol‐specific HSF1–HSF2 heterocomplexes. This perturbs the in vivo binding of HSF2 to heat shock elements (HSEs) in genes that control neuronal migration in normal conditions, such as p35 or the MAPs(microtubule‐associated proteins, such as Dclk1 and Dcx), and alters their expression. In the absence of HSF2, migration defects as well as alterations in gene expression are reduced. Thus, HSF2, as a sensor for alcohol stress in the fetal brain, acts as a mediator of the neuronal migration defects associated with FASD

Developmentally Regulated Chromosome Fragmentation Linked to Imprecise Elimination of Repeated Sequences in Paramecia

The chromosomes of ciliates are fragmented at reproducible sites during the development of the polyploid somatic macronucleus, but the mechanisms involved appear to be quite diverse in different species. In Paramecium aurelia, the process is imprecise and results in de novo telomere addition at locally heterogeneous positions. To search for possible determinants of chromosome fragmentation, we have studied an ∼21-kb fragmentation region from the germ line genome of P. primaurelia. The mapping and sequencing of alternative macronuclear versions of the region show that two distinct multicopy elements, a minisatellite and a degenerate transposon copy, are eliminated by an imprecise mechanism leading either to chromosome fragmentation and the formation of new telomeres or to the rejoining of flanking sequences. Heterogeneous internal deletions occur between short direct repeats containing TA dinucleotides. The complex rearrangement patterns produced vary slightly among genetically identical cell lines, show non-Mendelian inheritance during sexual reproduction, and can be experimentally modified by transformation of the maternal macronucleus with homologous sequences. These results suggest that chromosome fragmentation in Paramecium is the consequence of imprecise DNA elimination events that are distinct from the precise excision of single-copy internal eliminated sequences and that target multicopy germ line sequences by homology-dependent epigenetic mechanisms

High coding density on the largest Paramecium tetraurelia somatic chromosome.

Paramecium, like other ciliates, remodels its entire germline genome at each sexual generation to produce a somatic genome stripped of transposons and other multicopy elements. The germline chromosomes are fragmented by a DNA elimination process that targets heterochromatin to give a reproducible set of some 200 linear molecules 50 kb to 1 Mb in size. These chromosomes are maintained at a ploidy of 800n in the somatic macronucleus and assure all gene expression. We isolated and sequenced the largest megabase somatic chromosome in order to explore its organization and gene content. The AT-rich (72%) chromosome is compact, with very small introns (average size 25 nt), short intergenic regions (median size 202 nt), and a coding density of at least 74%, higher than that reported for budding yeast (70%) or any other free-living eukaryote. Similarity to known proteins could be detected for 57% of the 460 potential protein coding genes. Thirty-two of the proteins are shared with vertebrates but absent from yeast, consistent with the morphogenetic complexity of Paramecium, a long-standing model for differentiated functions shared with metazoans but often absent from simpler eukaryotes. Extrapolation to the whole genome suggests that Paramecium has at least 30,000 genes

Ex post evaluation of the activities of the joint research centre under Horizon 2020 and Euratom 2014-2020

The report is the result of the external Panel ex post evaluation of the JRC activities under H2020 and Euratom 2014-2020. It provides the independent assessment requested in the Council Decisions concerning the specific programmes to be carried out by means of direct actions by the Joint Research Centre implementing the Horizon 2020 Framework Programme (2014-2020) of the European Commission and of the European Atomic Energy Community (Euratom). The evaluation has been conducted by a panel of independent external experts under the chairmanship of Dr Rolf-Dieter Heuer. In this report the Panel concludes positively on the effectiveness of the JRC as the Commission’s science service in support of Euratom and EU policies. Besides a number of recommendations for incremental improvement of the JRC, the Panel has flagged that the JRC is in a unique position as a provider of independent scientific evidence inside the European Commission, but, because of this, the JRC and its research work are less visible to the outside world than they merit. The Panel also flags that the JRC and its stakeholders, internal and external to the Commission, would also benefit from more communication and interactions. The Panel has particularly appreciated the meetings with the stakeholders that gave much insight into the cooperation between the JRC and the other parts of the Commission, supporting our positive assessment and our suggestions for improvement

Translational control of intron splicing in eukaryotes

LettersInternational audienc

The paramecium germline genome provides a niche for intragenic parasitic DNA: evolutionary dynamics of internal eliminated sequences

Insertions of parasitic DNA within coding sequences are usually deleterious and are generally counter-selected during evolution. Thanks to nuclear dimorphism, ciliates provide unique models to study the fate of such insertions. Their germline genome undergoes extensive rearrangements during development of a new somatic macronucleus from the germline micronucleus following sexual events. In Paramecium, these rearrangements include precise excision of unique-copy Internal Eliminated Sequences (IES) from the somatic DNA, requiring the activity of a domesticated piggyBac transposase, PiggyMac. We have sequenced Paramecium tetraurelia germline DNA, establishing a genome-wide catalogue of ~45,000 IESs, in order to gain insight into their evolutionary origin and excision mechanism. We obtained direct evidence that PiggyMac is required for excision of all IESs. Homology with known P. tetraurelia Tc1/mariner transposons, described here, indicates that at least a fraction of IESs derive from these elements. Most IES insertions occurred before a recent whole-genome duplication that preceded diversification of the P. aurelia species complex, but IES invasion of the Paramecium genome appears to be an ongoing process. Once inserted, IESs decay rapidly by accumulation of deletions and point substitutions. Over 90% of the IESs are shorter than 150 bp and present a remarkable size distribution with a ~10 bp periodicity, corresponding to the helical repeat of double-stranded DNA and suggesting DNA loop formation during assembly of a transpososome-like excision complex. IESs are equally frequent within and between coding sequences; however, excision is not 100% efficient and there is selective pressure against IES insertions, in particular within highly expressed genes. We discuss the possibility that ancient domestication of a piggyBac transposase favored subsequent propagation of transposons throughout the germline by allowing insertions in coding sequences, a fraction of the genome in which parasitic DNA is not usually tolerated. Author Summary Top Ciliates are unicellular eukaryotes that rearrange their genomes at every sexual generation when a new somatic macronucleus, responsible for gene expression, develops from a copy of the germline micronucleus. In Paramecium, assembly of a functional somatic genome requires precise excision of interstitial DNA segments, the Internal Eliminated Sequences (IES), involving a domesticated piggyBac transposase, PiggyMac. To study IES origin and evolution, we sequenced germline DNA and identified 45,000 IESs. We found that at least some of these unique-copy elements are decayed Tc1/mariner transposons and that IES insertion is likely an ongoing process. After insertion, elements decay rapidly by accumulation of deletions and substitutions. The 93% of IESs shorter than 150 bp display a remarkable size distribution with a periodicity of 10 bp, the helical repeat of double-stranded DNA, consistent with the idea that evolution has only retained IESs that can form a double-stranded DNA loop during assembly of an excision complex. We propose that the ancient domestication of a piggyBac transposase, which provided a precise excision mechanism, enabled transposons to subsequently invade Paramecium coding sequences, a fraction of the genome that does not usually tolerate parasitic DNA. Citation: Arnaiz O, Mathy N, Baudry C, Malinsky S, Aury J-M, et al. (2012) The Paramecium Germline Genome Provides a Niche for Intragenic Parasitic DNA: Evolutionary Dynamics of Internal Eliminated Sequences. PLoS Genet 8(10): e1002984. doi:10.1371/journal.pgen.1002984 Editor: Harmit S. Malik, Fred Hutchinson Cancer Research Center, United States of America Received: March 16, 2012; Accepted: August 9, 2012; Published: October 4, 2012 Copyright: © Arnaiz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the ANR BLAN08-3_310945 “ParaDice,” the ANR 2010 BLAN 1603 “GENOMAC,” a CNRS ATIP-Plus grant to MB (2010–2011), and an “Equipe FRM” grant to EM. The sequencing was carried out at the Genoscope - Centre National de Séquençage (Convention GENOSCOPE-CEA number 128/AP 2007_2008/CNRS number 028666). CDW and AM were supported by Ph.D. fellowships from the Ministère de l'Enseignement Supérieur et de la Recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Terres inhospitalières

Certains milieux sont réputés avoir été colonisés, ou pas, par les sociétés humaines tout au long de l’histoire. Selon les périodes, les conditions environnementales et les types de sociétés, il peut s’agir des bandes côtières, des massifs montagneux, des zones marécageuses… Ces zones se révèlent parfois plus intensément habitées et fréquentées que prévu. Some environments are believed to have been colonized, or not, by human societies throughout history. Depending on the period, on environmental conditions and types of societies, these environments may be coastal strips, mountains, swampy areas ... These areas are sometimes more densely inhabited and busy than expected. Se sabe que algunos entornos han sido colonizados, o no, por las sociedades humanas a través de la historia. Según la época, las condiciones ambientales y el tipo de sociedad, pueden ser franjas costeras, cordilleras, zonas pantanosas, etc. Estas zonas a veces resultan ser más intensamente habitadas y frecuentadas de lo previsto